Roux-en-Y gastric bypass (RYGB) is a form of bariatric surgery that is widely performed for medically complicated obesity and that cures type 2 diabetes in 85% of cases. The physiologic mechanisms mediating diabetes resolution are controversial, but it is believed that the incretin hormone glucagon-like peptide-1 (GLP-1) may play an important role. GLP-1 stimulates the secretion of insulin by pancreatic beta cells and is responsible for the “incretin” effect: incretin hormones enhance the glucose-dependent secretion of insulin, such that pancreatic beta cells will secrete more insulin after an oral glucose load than after an isoglycemic IV glucose load. Enhanced secretion of GLP-1 after RYGB, and a resultant elevation in insulin secretion, may play a primary role in the resolution of diabetes after RYGB.
However, as the use of bariatric surgical procedures continues to increase worldwide, a severe complication—hyperinsulinemic hypoglycemia—is increasingly reported. This disorder manifests in 1-6% of RYGB patients, and leads to severe symptomatic hypoglycemia, often multiple times daily, characterized by glucose concentrations low enough (20-40 mg/dL) to cause seizures, altered mental status, loss of consciousness, cognitive dysfunction, disability, and death. Quality of life is severely diminished, and many patients cannot care for themselves or others, work, drive, or be left unaccompanied. Currently there is no satisfactory treatment for hyperinsulinemic hypoglycemia. Severe cases have been managed with near-total to total pancreatectomy, which results in insulin-dependent diabetes and is associated with a 6% surgical mortality risk. There continues to be a need for a therapy that safely and effectively mitigates hyperinsulinemic hypoglycemia.